ABSTRACT-The inhibitory effect of olopatadine, a new antiallergic drug, on antigen-induced eosinophil infiltration and its mechanisms were examined using the local sensitized rat allergic rhinitis model and isolated IL-5-stimulated rat peritoneal eosinophils. Olopatadine dose-dependently inhibited antigen-induced eosinophil infiltration in the nasal mucosa. Olopatadine dose-dependently repressed the IL-5-induced expressions of CD11a / CD18 (LFA-1) and CD11b / CD18 (Mac-1) on rat peritoneal eosinophils. However, olopatadine had no effect on IL-5-induced CD49d/ CD29 (VLA-4) expression. These results suggest that olopatadine may inhibit antigen-induced eosinophil infiltration through repression of LFA-1 and Mac-1 expression. Keywords: Eosinophil infiltration, Allergic rhinitis, Adhesion moleculeAllergic rhinitis is an inflammatory disorder of the nose characterized by symptoms of sneezing, rhinorrhea and nasal congestion after allergen exposure. In most cases, allergic rhinitis has two phases that are known as the immediate phase and the late phase. The immediate phase is triggered by an IgE-mediated anaphylactic reaction by inhaled allergens (1). In contrast, the late phase reaction is typically referred to as a spontaneous recurrence of symptoms about 12 h after the immediate phase reaction (2). During the late phase, many eosinophils, which can be the source of IL-4, IL-5 (3), leukotriene, and superoxide anion (4), are infiltrated into nasal mucosa. A hallmark of allergic rhinitis is an increased number of eosinophils in the rhinitic nose compared with non-allergic subjects.Olopatadine (KW-4679), (Z)-11-[(3-dimethylamino) propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid monohydrochloride, is a new antiallergic drug. This compound has been shown to be a specific H1 histamine-receptor antagonist with a K i value of 16 nM (5); and it has been shown to suppress leukotrienes (LTs) and thromboxane (TX) release and platelet-activating factor (PAF) formation by reducing arachidonic acid release from phospholipids in guinea pig eosinophils (6).In the present study, we examined the effect of olopatadine on antigen-induced eosinophil infiltration into nasal mucosa using the local sensitized rat allergic rhinitis model and investigated the influence of this compound on the expression of adhesion molecules on the surface of eosinophils.Male Brown Norway (BN) rats weighing 180 -230 g were provided by Charles River Japan (Kanagawa). The animals were housed in an air-conditioned room maintained at 25 ± 1°C with humidity of 55 ± 5% and a 12-h light / dark cycle for 1 week before the commencement of experiments. Food and water were provided ad libitum. Ovalbumin (OA; Sigma Chemical Co., St. Louis, MO, USA) was used as the antigen. BN rats were sensitized in our original cages (Fig. 1) that could be circulated with OA (0.2 g/ day) all day. In preliminary experiments, we established that the dose of OA used in this study did not elicit any detectable bronchoconstriction (data not shown). Each experimental group consisted of...
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